Tumor- and Radiation-Related Complications after Ruthenium-106 Brachytherapy in Small to Medium Uveal Melanomas (Part 1)

Abstract

Purpose The purpose of this study was to analyze tumor-related complications after ruthenium-106 brachytherapy in patients with uveal melanoma, with respect to local tumor control, insufficient radiation response, enucleation, and metastasis rate.

Patients/Methods and Materials This retrospective study included 608 patients treated consecutively with ruthenium-106 brachytherapy between January 2008 and December 2010 at the Department of Ophthalmology, University Hospital Essen. The occurrence of radiation-induced results was analyzed by estimating the risk by applying the Kaplan-Meier method, i.e., the “time to event” analysis. The Cox model test was used for the univariate and multivariate risk factor analyses. The median follow-up was 51 months after primary treatment.

Results Tumor recurrence was found in 21 patients (3.5%) and repeated treatment due to insufficient effect after the initial ruthenium-106 brachytherapy was performed in 40 patients (6.6%). The 5-year cumulative risk of recurrence was 4.0% and that of insufficient effect was 7.3%. Thirteen patients (2.1%) underwent a secondary enucleation; 8 because of a local recurrence and 5 because of severe post-brachytherapy complications. The cumulative enucleation risk was 2.3% after 5 years and 2.9% after 10 years, corresponding to eye preservation of 97.7 and 97.1%, respectively. In forty-two patients (7.2%), metastatic disease was diagnosed during the follow-up. The metastatic rate as calculated by the Kaplan-Meier method was 9.0, and 13.1% at 5 and 10 years, respectively.

Conclusion Our study demonstrated that ruthenium-106 brachytherapy is an excellent treatment option for achieving local tumor control and eye preservation in well-selected patients. The metastatic rate is in agreement with that of previous studies analyzing small to medium size uveal melanomas.

Zusammenfassung

Ziel Das Ziel dieser Studie war die Analyse tumor- und strahlenbedingter Komplikationen nach Ruthenium-106-Brachytherapie bei Patienten mit Aderhautmelanom hinsichtlich lokaler Tumorkontrolle, unzureichender Strahlenreaktion, Enukleationsrate und Metastasierungsrate.

Patienten/Methoden und Materialien Diese retrospektive Studie umfasste 608 Patienten, die zwischen Januar 2008 und Dezember 2010 an der Augenklinik des Universitätsklinikums Essen mit Ruthenium-106-Brachytherapie behandelt wurden. Das Auftreten strahleninduzierter Ergebnisse wurde durch Risikoabschätzung mithilfe der Kaplan-Meier-Methode, d. h. der „Time-to-Event“-Analyse, analysiert. Für die univariate und multivariate Risikofaktoranalyse wurde der Cox-Modelltest verwendet. Die mittlere Nachbeobachtungszeit betrug 51 Monate nach der Erstbehandlung.

Ergebnisse Bei 21 Patienten (3,5%) wurde ein Tumorrezidiv festgestellt und bei 40 Patienten (6,6%) wurde eine wiederholte Behandlung aufgrund eines unzureichenden Effekts nach der primären Ruthenium-106-Brachytherapie durchgeführt. Das kumulative 5-Jahres-Risiko eines Rezidivs betrug 4,0% und dasjenige eines unzureichenden Effekts 7,3%. 13 Patienten (2,1%) wurden einer sekundären Enukleation unterzogen: 8 wegen eines Lokalrezidivs und 5 wegen schwerer Komplikationen nach der Brachytherapie. Das kumulative Enukleationsrisiko betrug 2,3% nach 5 Jahren und 2,9% nach 10 Jahren, was einer Augenerhaltung von 97,7% bzw. 97,1% entspricht. Bei 42 Patienten (7,2%) wurde während der Nachbeobachtungszeit eine Metastasierung diagnostiziert. Die mithilfe der Kaplan-Meier-Methode berechnete Metastasierungsrate betrug 9,0% bzw. 13,1% nach 5 und 10 Jahren, entsprechend.

Fazit Unsere Studie hat gezeigt, dass die Ruthenium-106-Brachytherapie eine hervorragende Behandlungsoption zur Erzielung einer lokalen Tumorkontrolle und zum Augenerhalt bei gut ausgewählten Patienten ist. Die Metastasierungsrate stimmt mit der in früheren Studien überein, in denen kleine bis mittelgroße Aderhautmelanome analysiert wurden.

Conclusion Box

Already known:

• Plaque brachytherapy has been used for the treatment of UM for almost 60 years and is considered an effective method for local tumor control and eye preservation.

• The survival benefit for patients with UM treated with brachytherapy is under debate.

• This retrospective study aimed to investigate the efficacy of ruthenium-106 brachytherapy.

Newly described:

• This retrospective study aimed to investigate the efficacy of ruthenium-106 brachytherapy dependent on tumor baseline characteristics and radiation dosage.

• Indices of tumor- and radiation-related complications were acceptable and comparable with those in the existing literature. The 5-year recurrence rate was 4% and the metastatic rate was 9.0 and 13.1% at 5 and 10 years, respectively.

• Overall, this study demonstrates that ruthenium-106 brachytherapy is an excellent treatment option for well-selected patients with UM.

Keywords

uveal melanoma - 106-ruthenium - brachytherapy - epidemiology - choroid - ocular tumors - retina

Schlüsselwörter

Aderhautmelanom - 106-Ruthenium - Brachytherapie - Epidemiologie - Chorioidea - okuläre Tumoren - Retina

Publication History

Received: 15 November 2023

Accepted: 13 February 2024

Accepted Manuscript online:
14 February 2024

Article published online:
04 April 2024

• References

• 1 Kaliki S, Shields CL. Uveal melanoma: relatively rare but deadly cancer. Eye (Lond) 2017; 31: 241-257
• 2 Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology 2011; 118: 1881-1885
• 3 Virgili G, Gatta G, Ciccolallo L. et al. Incidence of uveal melanoma in Europe. Ophthalmology 2007; 114: 2309-2315
• 4 Lommatzsch PK. Results after beta-irradiation (106Ru/106Rh) of choroidal melanomas: 20 yearsʼ experience. Br J Ophthalmol 1986; 70: 844-851
• 5 Stallard HB. Radiotherapy for malignant melanoma of the choroid. Br J Ophthalmol 1966; 50: 147-155
• 6 American Brachytherapy Society – Ophthalmic Oncology Task Force. Electronic address: [e-mail], ABS – OOTF Committee. The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma. Brachytherapy 2014; 13: 1-14
• 7 Lommatzsch P, Vollmar R. [A new way in the conservative therapy of intraocular tumors by means of beta-irradiation (Ruthenium 106) with preservation of vision]. Klin Monbl Augenheilkd 1966; 148: 682-699
• 8 Brualla L, Sempau J, Zaragoza FJ. et al. Accurate estimation of dose distributions inside an eye irradiated with 106Ru plaques. Strahlenther Onkol 2013; 189: 68-73
• 9 Manschot WA, van Peperzeel HA. Choroidal melanoma. Enucleation or observation? A new approach. Arch Ophthalmol 1980; 98: 71-77
• 10 McLean IW, Foster WD, Zimmerman LE. et al. Inferred natural history of uveal melanoma. Invest Ophthalmol Vis Sci 1980; 19: 760-770
• 11 Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch Ophthalmol 2006; 124: 1684-1693
• 12 Flühs D, Bambynek M, Heintz M. et al. Dosimetry and design of radioactive eye plaques. Front Radiat Ther Oncol 1997; 30: 26-38
• 13 Stannard C, Sauerwein W, Maree G. et al. Radiotherapy for ocular tumours. Eye (Lond) 2013; 27: 119-127
• 14 Stöckel E, Eichmann M, Flühs D. et al. Dose distributions and treatment margins in ocular brachytherapy with ¹⁰⁶Ru eye plaques. Ocul Oncol Pathol 2018; 4: 122-128
• 15 Thomson RM, Furutani KM, Kaulich TW. et al. AAPM recommendations on medical physics practices for ocular plaque brachytherapy: Report of task group 221. Med Phys 2020; 47: e92-e124
• 16 Zaragoza FJ, Eichmann M, Flühs D. et al. Monte Carlo estimation of absorbed dose distributions obtained from heterogeneous ¹⁰⁶Ru eye plaques. Ocul Oncol Pathol 2017; 3: 204-209
• 17 Damato B, Patel I, Campbell IR. et al. Local tumor control after 106Ru brachytherapy of choroidal melanoma. Int J Radiat Oncol Biol Phys 2005; 63: 385-391
• 18 Frenkel S, Hendler K, Peʼer J. Uveal melanoma in Israel in the last two decades: characterization, treatment and prognosis. Isr Med Assoc J 2009; 11: 280-285
• 19 Gragoudas E, Li W, Goitein M. et al. Evidence-based estimates of outcome in patients irradiated for intraocular melanoma. Arch Ophthalmol 2002; 120: 1665-1671
• 20 Jampol LM, Moy CS, Murray TG. et al. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: IV. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS report no. 19. Ophthalmology 2002; 109: 2197-2206
• 21 Karlsson UL, Augsburger JJ, Shields JA. et al. Recurrence of posterior uveal melanoma after ⁶⁰Co episcleral plaque therapy. Ophthalmology 1989; 96: 382-388
• 22 Rouberol F, Roy P, Kodjikian L. et al. Survival, anatomic, and functional long-term results in choroidal and ciliary body melanoma after ruthenium brachytherapy (15 yearsʼ experience with beta-rays). Am J Ophthalmol 2004; 137: 893-900
• 23 Shields CL, Shields JA, Karlsson U. et al. Reasons for enucleation after plaque radiotherapy for posterior uveal melanoma. Clinical findings. Ophthalmology 1989; 96: 919-923
• 24 Verschueren KM, Creutzberg CL, Schalij-Delfos NE. et al. Long-term outcomes of eye-conserving treatment with Ruthenium¹⁰⁶ brachytherapy for choroidal melanoma. Radiother Oncol 2010; 95: 332-338
• 25 Salkola S, Heikkonen J, Eskelin S. et al. Management of choroidal melanomas less than 10 mm in largest basal diameter with a 10-mm ruthenium plaque. Retina 2014; 34: 2110-2120
• 26 Kaiserman I, Anteby I, Chowers I. et al. Post-brachytherapy initial tumor regression rate correlates with metastatic spread in posterior uveal melanoma. Br J Ophthalmol 2004; 88: 892-895
• 27 Diener-West M, Earle JD, Fine SL. et al. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18. Arch Ophthalmol 2001; 119: 969-982
• 28 Summanen P, Immonen I, Heikkonen J. et al. Survival of patients and metastatic and local recurrent tumor growth in malignant melanoma of the uvea after ruthenium plaque radiotherapy. Ophthalmic Surg 1993; 24: 82-90
• 29 Vrabec TR, Augsburger JJ, Gamel JW. et al. Impact of local tumor relapse on patient survival after cobalt 60 plaque radiotherapy. Ophthalmology 1991; 98: 984-988
• 30 Caujolle JP, Paoli V, Chamorey E. et al. Local recurrence after uveal melanoma proton beam therapy: recurrence types and prognostic consequences. Int J Radiat Oncol Biol Phys 2013; 85: 1218-1224